Cirrhosis is the fourth leading cause of death in the United States in individuals under the age of 65, the productive years of life. It affects men and women equally, and impacts on all races and socio- economical levels. Portal hypertension is the main complication of cirrhosis, regardless of etiology. Gastroesophageal varices and variceal hemorrhage are a direct consequence of portal hypertension and account in large part for the high mortality of cirrhosis. Varices result from porto-systemic collaterals that develop as portal pressure increases. Non-selective beta-adrenergic blockers decrease portal pressure and have been shown to prevent the first variceal hemorrhage in patients with cirrhosis and varices. However, a beneficial effect on survival has not been clearly demonstrated. This is probably related to the advanced stage of cirrhosis at the time beta- blocker therapy is initiated, since in these studies patients already have varices and frequently have ascites. Experimental studies have shown that propranolol therapy, administered in the early stages of portal hypertension, can prevent the development of porto-systemic collaterals. Early portal hypotensive therapy would be beneficial not only because it may prevent or delay the formation of varices (and consequently of variceal hemorrhage), but because it may prevent or delay the development of other complications of portal hypertension, such as ascites and porto-systemic encephalopathy. This trial is designed as a prospective, randomized, placebo-controlled, double-blind trial of 212 patients with cirrhosis and portal hypertension. Its primary aim is to investigate if early beta-adrenergic therapy can prevent or delay the development of gastroesophageal varices in patients with cirrhosis and portal hypertension. Secondary aims will examine whether this therapy prevents or delays other complications of portal hypertension such as ascites and porto-systemic encephalopathy, as well as liver transplantation or death. Patients with cirrhosis, without varices on endoscopy and with a portal pressure of greater than or equal to 6 mmHg will be included and will be followed for up to 5 years. In planning the trial, we assumed a rate of development of varices of 50% at 4 years. The calculated sample size of 2123 ensures high statistical power (80%) to detect a reduction in varices to 30% in the propranolol group. The trial is highly significant for the promise it holds for the treatment of cirrhosis of all etiologies and for an understanding of the natural history of the disease. The four centers involved are widely renown for their studies in this area and have collaborated productively in the past, including the only published double-blind trial of propranolol in the prevention of first variceal hemorrhage in patients with cirrhosis and varices.